Non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel by proton-pump inhibitors

A pilot study

Jen Kuang Lee, Cho Kai Wu, Jyh Ming Juang, Chia Ti Tsai, Juey Jen Hwang, Jiuun Lee Lin, Fu Tien Chiang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and protonpump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods: Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping™ (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results: Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions: Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalActa Cardiologica Sinica
Volume32
Issue number2
DOIs
Publication statusPublished - Mar 1 2016
Externally publishedYes

Fingerprint

clopidogrel
Proton Pump Inhibitors
Blood Platelets
Alleles
Thrombelastography
Therapeutic Uses
Platelet Aggregation
Pharmaceutical Preparations
Healthy Volunteers
Randomized Controlled Trials
Cytochrome P-450 CYP2C19

Keywords

  • Clopidogrel
  • CYP2C19 polymorphism
  • Platelet aggregation
  • Proton pump inhibitors
  • TEG
  • VASP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel by proton-pump inhibitors : A pilot study. / Lee, Jen Kuang; Wu, Cho Kai; Juang, Jyh Ming; Tsai, Chia Ti; Hwang, Juey Jen; Lin, Jiuun Lee; Chiang, Fu Tien.

In: Acta Cardiologica Sinica, Vol. 32, No. 2, 01.03.2016, p. 215-222.

Research output: Contribution to journalArticle

Lee, Jen Kuang ; Wu, Cho Kai ; Juang, Jyh Ming ; Tsai, Chia Ti ; Hwang, Juey Jen ; Lin, Jiuun Lee ; Chiang, Fu Tien. / Non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel by proton-pump inhibitors : A pilot study. In: Acta Cardiologica Sinica. 2016 ; Vol. 32, No. 2. pp. 215-222.
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abstract = "Background: The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and protonpump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods: Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping™ (TEG{\circledR}) and vasodilator-stimulated phosphoprotein (VASP) assays. Results: Both TEG{\circledR} and VASP tests showed the same general qualitative trend, but TEG{\circledR} detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG{\circledR} results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions: Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome.",
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AU - Wu, Cho Kai

AU - Juang, Jyh Ming

AU - Tsai, Chia Ti

AU - Hwang, Juey Jen

AU - Lin, Jiuun Lee

AU - Chiang, Fu Tien

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AB - Background: The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and protonpump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods: Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping™ (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results: Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions: Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome.

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